Translumbosacral Neuromodulation for FI

Summary

Fecal Incontinence (FI) affects 40 million Americans, predominantly women and elderly. It is a major health care burden, significantly impairs quality of life and psychosocial function. FI is characterized by multifactorial dysfunction including lumbosacral neuropathy, anorectal sensori-motor dysfunction, and abnormal pelvic floor-brain innervation. A critical barrier to progress in the treatment of FI is the lack of RCTs, absence of mechanistically based non-invasive therapies that modify disease, and a lack of understanding on how treatments affect pathophysiology of FI. Consequently, most current remedies remain ineffective. Our long-term goal is to address the problem of lack of effective treatments for FI by investigating treatments that modulate neuronal perturbations and thereby improve sensory and motor control, and to understand the neurobiologic basis of these treatments. Our central hypothesis is that a novel, non-invasive treatment consisting of Translumbosacral Neuromodulation Therapy (TNT), using repetitive magnetic stimulation, will significantly improve FI in the short-term and long-term, by enhancing neural excitability and inducing neuroplasticity. Our approach is based on compelling pilot study which showed that TNT at 1 Hz frequency, significantly improved FI, by enhancing bidirectional gut- brain signaling, anal sphincter strength and rectal sensation compared to 5 or 15 Hz. Our objectives are to 1) investigate the efficacy, safety and optimal dose of a new treatment, TNT, in a sham controlled, randomized dose-dependent study in 132 FI patients; 2) determine the mechanistic basis for TNT by assessing the efferent and afferent pelvic floor-brain signaling, and sensori-motor function; 3) identify the durability of treatment response and effects of TNT, and whether reinforcement TNT provides augmented improvement, by performing a long-term, sham controlled randomized trial. Our expected outcomes include the demonstration of TNT as a durable, efficacious, safe, mechanistically based, non-invasive, and low risk treatment for FI. The impact of our project includes a novel, disease modifying, non-invasive treatment, a scientific basis for this treatment, and improved understanding of the pathophysiology of FI and how TNT modifies bidirectional gut and brain axes and anorectal function. Ultimately, the knowledge generated by this project will provide new avenues for the development of innovative, evidence-based therapies for FI.

Conditions

• Fecal Incontinence

Interventions

DEVICE

Translumbosacral Neuromodulation Therapy (TNT)

A probe with 2 pairs of bipolar steel ring electrodes, will be placed in the rectum. At each site a mapping procedure is performed with single stimulus coil to assess the motor threshold intensity, defined as the minimum level of magnetic stimulation intensity required to achieve an anal and rectal MEP response of 10 microvolts and an anterior tibialis MEP of 20 microvolts with 50% of trials.The intensity for TNT at each site is capped at a maximum of 150% above this threshold to comply with safety guidelines. Thus, intensity of magnetic stimulations will be individualized. Bilateral lumbar stimulations (rTLMS) are administered at L2/L3 disc space, and sacral stimulations (rTSMS) at S2/S3 level. Next a 70 mm double air film self-cooling coil is positioned randomly over one of the 4 sites, held in place by a coil fixator and 300 or 450 stimulations are delivered. After a 5 min rest the cycle is repeated (Total =600-900/site).The coil is moved to the opposite side and it is repeated.

OTHER

Sham TNT Therapy

This is the sham TNT treatment as mentioned in the different ARMs using the fake coil with no magnetic stimulations.

Sponsors & Collaborators

• National Institutes of Health (NIH)

  collaborator NIH

• Massachusetts General Hospital

  collaborator OTHER

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Augusta University

  lead OTHER

Principal Investigators

• Satish Rao, MD,PhD · Augusta University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2019-06-05

Primary Completion

2024-02-29

Completion

2025-02-28

FDA Device

Yes

Countries

• United States

Study Locations